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Multiple regression analysis of pharmacogenetic variability of carvedilol disposition in 54 healthy Japanese volunteers.

The aim of this study was to evaluate the pharmacogenetic variability in the disposition of carvedilol in the Japanese population. Five or 10 mg of carvedilol was orally administered to 54 healthy Japanese subjects (22-44 years old), and blood samples were taken at 2 and 6 h after dosing. We determined the polymorphic alleles of CYP2D6, CYP2C9, CYP2C19, CYP3A5, UGT2B7, and MDR1 in each subject. The whole blood concentration of R- and S-carvedilol was measured by an HPLC method. The pharmacokinetic parameters in individual subjects were estimated by the Bayesian method using the nonlinear mixed effects model (NONMEM) program. We then examined the effect of the genetic polymorphisms on the variability in the pharmacokinetics of carvedilol using a multiple regression analysis. The oral clearance (CL/F) and also apparent volume of distribution (V/F) of both enantiomers were significantly lower in the subjects with the CYP2D6*10 allele than those with the CYP2D6*1/*1, *1/*2, or *2/*2 genotype, confirming our previous finding that the bioavailability (F) and systemic clearance (CL) of R- and S-carvedilol in the liver is significantly altered in Japanese with the CYP2D6*10 allele. On the other hand, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP3A5*3, UGT2B7*2, and MDR1 C3435T did not significantly affect the pharmacokinetics of carvedilol in Japanese subjects.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Multiple regression analysis of diagnostic predictors in optic nerve disease.

Demyelination is assumed to be the cause of the majority of cases of isolated optic neuritis. Because of the importance of establishing the presence of optic nerve dysfunction in patients suspected of having multiple sclerosis several new indices of optic nerve conduction have been reported including the visual evoked potential, the edge-light pupil cycle time, and the Pulfrich test. These measures purport to detect optic nerve dysfunction but with varying degrees of success. This study of 93 patients with clearly documented previous optic neuritis was conducted to determine the statistical relationship between these three measures and other clinical diagnostic indices for detection for previous optic nerve disease and the utility of the diagnostic predictors taken individually, and in combination. The other indices used were the presence of detectable optic atrophy, color vision defect and the presence of a relative afferent pupillary defect. The variables were submitted to linear stepwise multiple regression analysis which indicated that the presence of optic atrophy, defective color vision and prolonged pupil cycle time when used in combination provided the most useful diagnostic prediction of previous optic neuritis in this group of patients. The addition of visual evoked potentials, the Pulfrich test or presence of a relative afferent pupillary defect did not significantly increase predictive reliability.

Adolescent↗

[A study on health examination services under the Health Service Law for the Aged--multiple logistic regression analysis of service methods and the service-acceptance rate].

A survey on health services provided in accordance with the Health Service Law for the Aged was conducted in 3,278 cities, wards, towns, and villages throughout Japan in May 1985. Responses were returned from 2,645 districts and data on beneficiaries of these health services in 2,625 districts became available. Because the exact number of people constituting the subjects of health services could not be obtained, the service-acceptance rate was calculated by the number of people utilizing the services divided by the those in the population who were at least 40 years old. The service-acceptance rate was affected by both the size of the population of the local community and the methods of implementation of health services. Therefore, the mutual effects of population size and service methods were corrected by logistic regression analysis to find the relationship between methods of implementing health services and the response rate of the public in accepting the services. The service-acceptance rate was divided into two categories: one less than 30% and the other 30% and over. Odds ratios were calculated for an acceptance ratio of 30% and over. The results were summarized as follows: 1. In the jurisdictions where the local organizations cooperated in notifying citizens about the results of their general health examination, in comparison with the areas where there was no cooperation, the odds ratio was found to be 2.40. A similar comparison was made between the communities with local cooperation for notification of a general health examination and those communities without it. The odds ratio for the former was found to be 1.66.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Multiple regression analysis for assessing the growth of small hepatocellular carcinoma: the MIB-1 labeling index is the most effective parameter.

The aim of this study was to clarify whether histological parameters reflected tumor aggressiveness in patients with hepatocellular carcinoma (HCC). The tumor volume doubling times (TVDTs) of 21 HCCs, less than 3 cm in diameter at the start of the observation period, were calculated in 21 patients in whom the natural progression of the lesion was observed by ultrasonography. Paraffin-embedded sections were prepared from samples obtained by ultrasound-guided fine-needle liver biopsy at the end of the observation period. The histological parameters examined were the MIB-1 labeling index (LI), for which we performed immunohistochemical staining with the MIB-1 monoclonal antibody, using an antigen retrieval method; the nucleo-cytoplasmic (N/C ratio), cellularity, and the nuclear form factor (NFF), were calculated with an imaging analyzer. We performed multiple regression analysis for estimating the growth of small HCCs. With the N/C ratio (0.154 +/- 0.068; mean +/- SD), cellularity (453 +/- 21.8 cells/10(4) microm2), NFF (1.150 +/- 0.096), and degree of HCC differentiation as independent variables, only the MIB-1 LI (11.8 +/- 6.1%) showed a significant correlation with TVDT (207.5 +/- 162.6 days) (r = -0.658; P < 0.05). Compared to the conventional indices of histological atypism tested, i.e., N/C ratio, cellularity NFF, and degree of HCC differentiation, only MIB-1 LI was significantly correlated with small HCC growth rate. The MIB-1 LI may therefore be a simple and useful index of tumor aggressiveness.

Aged↗

[Importance of pre- and perinatal risk factors in respiratory distress syndrome of premature infants. A logical regression analysis of 1100 cases].

BACKGROUND: Respiratory distress syndrome (RDS) due to surfactant deficiency remains a cause of considerable mortality in the neonatal period. METHODS: In a retrospective study we analysed the records of 1109 premature newborns with a birth weight below 1500 g that were treated on our unit. RDS was assumed if the infants needed mechanical ventilation with oxygen supplementation and the typical radiological signs were present on chest x-ray. RESULTS: No changes in the incidence of RDS were found during the period of observation. Below 29 weeks gestational age 90% of infants suffered from RDS (55% severe RDS grade III or IV). The incidence was 75% (grade III or IV: 32%) for infants born at 29 and 30 weeks, 48% (grade III or IV: 15%) at 31 and 32 weeks and 33% (grade III or IV: 6%) for neonates born at 33 weeks of gestation. Using a logistic regression analysis model the following parameters were found to increase the risk for RDS significantly (p < 0.05): no prenatal steroid treatment, Cesarean section, male gender, APGAR at 5 min < 7, metabolic acidosis (base excess < or = -6 mval) and rectal temperature < 36 degrees C on admission. Following gestosis, insufficiency of the placenta and premature rupture of membranes a decrease in the incidence of RDS was observed. CONCLUSION: We conclude that although some risk factors for RDS will be difficult to exclude (e.g. maternal disease, gender) the incidence and severity of RDS can be reduced by measures like maternal antenatal steroid treatment. Perinatal asphyxia (low APGAR values and/or acidosis) and hypothermia should be avoided, as these conditions increase the relative risk for developing RDS.

Acidosis↗

Impact of age on QT interval and QT dispersion in healthy subjects: a regression analysis.

OBJECTIVE: although the isolated effects of age on QT interval and QT dispersion (QTd) have been previously investigated, no data are available on the simultaneous effects of age and other physiological or lifestyle factors on QT interval and QTd in healthy subjects. We studied the effects of age, gender, body mass index, smoking status, and blood pressure on these electrocardiographic parameters. DESIGN: observational study. SETTING: academic medical centre. PARTICIPANTS AND MEASUREMENTS: age, gender, body mass index, smoking status, and blood pressure were obtained from 191 consecutive healthy subjects (101 males and 90 females, age range 19-89 years). The subjects were divided into three groups according to their age: <30 (n=56), 30-65 (n=49), and >65 years (n=86). RESULTS: heart-rate corrected QT interval (QTc, Bazett's formula) progressively increased with advancing age (389+/-3 vs. 411+/-4 vs. 418+/-3 ms, means+/-SEM; P<0.01). By contrast, no differences in QTd were observed across the three groups (36+/-2 vs. 35+/-3 vs. 40+/-2 ms, P=NS). A multivariate regression analysis showed that age (P<0.01) and body mass index (P=0.04) independently predicted QT interval while gender was a weak (P=0.09) predictor of QTd. CONCLUSIONS: after adjusting for gender, smoking status, and blood pressure, age and body mass index independently predicted QT interval in healthy subjects. By contrast, age is not a predictor of QTd. The increase of QT interval associated with ageing and body mass index might be secondary to cardiac hypertrophy and myocardial action potential prolongation.

Adult↗

The treatment of mild hypertension in the elderly, a prospective study using multiple regression analysis.

In order to examine the effect of treatment of mild hypertension of the aged, a 4 year prospective trial was performed in 41 placebo and 38 drug-treated patients with an average age of 76.5 years. Patients were matched for blood pressure, sex and age. Patients with cardiovascular complications or blood pressure elevation above 200/110 were categorized as dropouts and totaled 17 cases (41.5%) in the placebo group, and 4 cases (10.5%) in the drug-treated group (p less than 0.01). In diastolic hypertension, dropouts formed 63.6% of the placebo group (mean BP, 170/92), and 9.5% of the drug group (mean BP, 179/94) (p less than 0.001). In systolic hypertension, dropouts were of 15.8% in the placebo group (mean BP, 164/79), and of 11.8% in the drug group (mean BP, 167/79), and no significant difference was observed. In the placebo group, dropouts were significantly higher in patients with pretreatment systolic blood pressure over 170 mmHg or diastolic blood pressure over 90 mmHg. In patients of 75 years of age or more, dropouts were 46.4% in the placebo group, and 13.0% in the drug treated group showing the beneficial effect of drug treatment even in those over the age of 75. However, no beneficial effect was observed over the age of 85. Stepwise multiple regression analysis of total case revealed that the greatest predictor for dropout was the presence of placebo (i.e. no treatment), explaining 12.2% of the variation in future dropout. Similarly, diastolic hypertension explained 7.5%, creatinine 6.7%, and age 4.6% of this variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Valuing avoided morbidity using meta-regression analysis: what can health status measures and QALYs tell us about WTP?

Many economists argue that willingness-to-pay (WTP) measures are most appropriate for assessing the welfare effects of health changes. Nevertheless, the health evaluation literature is still dominated by studies estimating nonmonetary health status measures (HSMs), which are often used to assess changes in quality-adjusted life years (QALYs). Using meta-regression analysis, this paper combines results from both WTP and HSM studies applied to acute morbidity, and it tests whether a systematic relationship exists between HSM and WTP estimates. We analyze over 230 WTP estimates from 17 different studies and find evidence that QALY-based estimates of illness severity--as measured by the Quality of Well-Being (QWB) Scale--are significant factors in explaining variation in WTP, as are changes in the duration of illness and the average income and age of the study populations. In addition, we test and reject the assumption of a constant WTP per QALY gain. We also demonstrate how the estimated meta-regression equations can serve as benefit transfer functions for policy analysis. By specifying the change in duration and severity of the acute illness and the characteristics of the affected population, we apply the regression functions to predict average WTP per case avoided.

Decision Making↗

A/C(i) curve analysis across a range of woody plant species: influence of regression analysis parameters and mesophyll conductance.

The analysis and interpretation of A/C(i) curves (net CO(2) assimilation rate, A, versus calculated substomatal CO(2) concentration, C(i)) is dependent upon a number of underlying assumptions. The influence of the C(i) value at which the A/C(i) curve switches between the Rubisco- and electron transport-limited portions of the curve was examined on A/C(i) curve parameter estimates, as well as the effect of mesophyll CO(2) conductance (g(m)) values on estimates of the maximum rate of Rubisco-mediated carboxylation (V(cmax)). Based on an analysis using 19 woody species from the Pacific Northwest, significant variation occurred in the C(i) value where the Rubisco- and electron transport-limited portions of the curve intersect (C(i_t)), ranging from 20 Pa to 152 Pa and averaging c. 71 Pa and 37 Pa for conifer and broadleaf species, respectively. Significant effects on estimated A/C(i) parameters (e.g. V(cmax)) may arise when preliminary estimates of C(i_t), necessary for the multiple regression analyses, are set either too high or too low. However, when the appropriate threshold is used, a significant relationship between A/C(i) and chlorophyll fluorescence estimates of carboxylation is achieved. The use of the V(cmax) parameter to describe accurately the Rubisco activity from the A/C(i) curve analysis is also dependent upon the assumption that C(i) is approximately equal to chloroplast CO(2) concentrations (C(c)). If leaf mesophyll conductance is low, C(c) will be much lower than C(i) and will result in an underestimation of V(cmax) from A/C(i) curves. A large range of mesophyll conductance (g(m)) values was observed across the 19 species (0.005+/-0.002 to 0.189+/-0.011 mol m(-2) s(-1) for Tsuga heterophylla and Quercus garryana, respectively) and, on average, g(m) was 1.9 times lower for the conifer species (0.058+/-0.017 mol m(-2) s(-1) for conifers versus 0.112+/-0.020 mol m(-2) s(-1) for broadleaves). When this mesophyll limitation was accounted for in V(cmax) estimates, considerable variation still existed between species, but the difference in V(cmax) between conifer and broadleaf species was reduced from c. 11 micromol m(-2) s(-1) to 4 micromol m(-2) s(-1). For example, A/C(i) curve estimates of V(cmax) were 31.2+/-6.2 and 42.2+/-4.4 micromol m(-2) s(-1), and A/C(c) curve estimates were 41.2+/-7.1 micromol m(-2) s(-1) and 45.0+/-4.8 micromol m(-2) s(-1), for the conifer and broadleaf species, respectively.

Biological Transport↗

Omnibus Budget Reconciliation Act of 1990 and voluntarism: logistic regression analysis of pharmacist responsibility.

OBJECTIVE: To examine the relationship between pharmacists' willingness to assume further professional responsibilities, as measured by attitudes to the Omnibus Budget Reconciliation Act of 1990 (OBRA '90) requirements, and their attitudes toward voluntarism as their responsibility to society and their level of interest in their jobs. DESIGN: A survey was distributed to a convenience sample of 443 pharmacists who were asked to indicate their responses on a number of items. SETTING: Surveys were distributed to participants in an annual pharmacy continuing education program. PARTICIPANTS: The response rate was 65 percent with completed surveys from 290 Florida pharmacists who were typically male (73 percent) and practicing in the community setting (39 percent) for over 25 years (33 percent). MAIN OUTCOMES: Questions were aimed at gathering the following information: (1) demographics; (2) attitudes concerning the benefits of the three OBRA '90 requirements: patient counseling, prospective drug-use review (DUR), and information recording; (3) attitudes toward voluntarism; and (4) job interest. RESULTS: Pharmacists tended to agree that all three of the OBRA '90 mandates will be beneficial. Fifty-six percent favored the prospective DUR requirements, while 68 percent favored the patient counseling requirements and 66 percent favored the information-recording requirements. Logistic regression analysis showed that unit increases in scaled responses, indicating more favorable attitudes toward believing that voluntarism was one's responsibility, increased the odds of favoring counseling by 38.7 percent and information recording by 32.4 percent. A similar directional relationship was found for the DUR requirement. Job interest did not add to the predictive ability of the variables already in the models. CONCLUSIONS: This study suggests a possible association between pharmacists' attitudes toward social responsibility and their acceptance of expanded professional responsibility.

Attitude of Health Personnel↗

[Perennial allergic rhinitis: stepwise regression analysis on the correlation with the efficacy of allergen-specific immunotherapy].

OBJECTIVE: To investigate the correlation factors of the immunotherapeutic efficiency of perennial allergic rhinitis (PAR). METHOD: One hundred and sixty-four patients with PAR were treated with specific immunotherapy (IT) in our department between 1990 and 2000. Specific allergens were selected through the history and skin test or nasal provocation test. The patients were given subcutaneous injections with allergen extract which was produced by Xiehe Hospital. The individual initiative dose was determined by the skin test reaction or the end point concentration. The doses were gradually increased until the maintenance dose (10(2) w/v, 0.5 ml once time), then the interval between injections was gradually increased up to one month. The clinical effectiveness evaluation based on the symptoms and signs before and after IT was judged as marked, moderated and poor response. The possible factors which affected the efficacy of IT were selected. These factors included sex, age, illness duration, disease condition, asthma, duration of IT, reaction condition of the skin test, accompanying itch of eye, ear and oral cavity, eosinophilia in nasal smears and family history of atopy. The correlation factors with efficacy were sifted with multifactorial stepwise regression analysis. RESULT: The marked, moderated and poor response were 14.4%, 54.3% and 31.3% respectively. The efficacy of IT correlated well with the duration of IT (P < 0.01), but not with sex, illness duration, disease condition, reaction condition of the skin test, accompanying itch of eye, ear and oral cavity, eosinophilia in nasal smears and family history of atopy. Asthma and age maybe influenced the effect of IT (P = 0.081, P = 0.063). CONCLUSION: This study demonstrates that the immunotherapy is effective in the treatment of perennial allergic rhinitis. The duration is the factor significantly influences the efficacy of IT. The efficacy of long-IT was superior to that of the short-IT.

Adolescent↗

[Studies on calcium oxalate crystal formation in urolithiasis. Multi-regressive analysis of urinary CaOx crystalline volumes and the effects of urinary various substances on CaOx crystal formation].

Because human urine contains various substances which can affect each other, it is quite difficult to clarify the mechanism of formation of calcium oxalate (CaOx) crystal in urine. The authors recently determined CaOx crystalline content and the concentrations of other substances in urine specimens from patients with urolithiasis and healthy volunteers, and subjected the data to multi-regressive analysis for the purpose of assessing the effect of these urinary substances on CaOx crystal formation. 1. In analysis of urine from patients with urolithiasis, the partial correlation coefficients of CaOx crystal formation with oxalic acid, sodium, calcium, uric acid magnesium were 0.67, 0.28, 0.18, and -0.10, respectively. The formula of regression was as follows: Amount of CaOx crystal (X 10(6) microns3/ml) = 3.59 X 10(-2) Ox (mM/L) + 4.72 X 10(-3) Ca (mM/L) + 4.52 X 10(-3) Na (mM/L) + 2.51 X 10(-4) UA (mM/L) -2.39 X 10(-2) Mg (mM/L) -1.65. The multiple correlation coefficient was 0.759. Thus, in patients with urolithiasis, urinary crystal formation was most dependent on the oxalic acid level, sodium, calcium, and uric acid were found to promote crystal formation, while magnesium to suppress it. 2. In analysis of urine from healthy volunteers, the partial correlation coefficients of CaOx crystal formation with oxalic acid and inorganic phosphorus were 0.51 and -0.24, respectively. The formula of regression was as follows: Amount of CaOx crystal (X 10(6) microns3/ml) = 1.91 X 10(-2) Ox (mM/L) -3.43 X 10(-4) P (mM/L) +0.29 The multiple correlation coefficient was 0.525.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗

Identification of persistent trophoblastic diseases based on a human chorionic gonadotropin regression curve by means of a stepwise piecewise linear regression analysis after the evacuation of uneventful moles.

Among the 191 patients with complete hydatidiform moles who were diagnosed and treated at Kyushu University Hospital from 1982 until 1996, 167 patients were diagnosed with uneventful moles retrospectively. The serial beta human chorionic gonadotropin (hCG) values in the 167 patients with uneventful moles were analyzed by a stepwise piecewise linear regression analysis in order to establish a normal regression curve of a human chorionic gonadotropin after a molar pregnancy. This normal regression curve is considered to be excellent regarding sensitivity (24/24-100%) and to be equivalent to the identification based on a plateau or a rise regarding specificity (156/167-93.4%). To distinguish patients with persistent trophoblastic disease (PTD) from uneventful moles, this normal curve is thus considered to be accurate since the accuracy was 180/191 (94. 2%). The weeks exceeding the normal regression curve in 24 PTD patients were 5.04 +/- 3.85 weeks and were also earlier than the weeks based on a plateau or a rise (P = 0.01). Within 7 weeks after evacuation, in 21/24 (87.5%) of the PTD cases, the beta-hCG values exceeded the normal range, while in only 14/24 (58.3%) the beta-hCG showed a change in the shape of a plateau or a rise. In addition, in 19/24 (79.2%) of the PTD patients, the time exceeding the normal range was shorter than the time exhibiting a plateau or a rise in the beta-hCG change. The above findings thus led us to conclude that this normal regression curve was useful for discriminating PTD from uneventful moles more precisely and more quickly than by identification based on a plateau or a rise.

Chorionic Gonadotropin↗

Estimation by regression analysis of endogenous amino acid levels in digesta collected from the distal ileum of pigs.

An experiment was conducted to estimate by simple linear regression the levels of endogenous amino acids in digesta collected from the distal ileum in pigs. Six barrows, average initial BW 35 kg, were fitted with a simple T-cannula at the distal ileum and fed six diets according to a 6 x 6 Latin square design. Six cornstarch-based diets containing six levels of CP from soybean meal (4, 8, 12, 16, 20, and 24% CP, respectively) were formulated. Chromic oxide (.4%) was included as the digestibility marker. Each experimental period consisted of 8 d. Ileal digesta were collected, at 2-h intervals, for a total of 24 h during d 7 and 8. There were linear relationships (P < .001) between dietary contents of apparent ileal digestible and total amino acids, irrespective of the ranges in graded dietary levels of amino acids. Determined with the regression technique, the endogenous levels of the indispensable amino acids (grams/kilogram of DMI) were as follows: arginine, .64; histidine, .23; isoleucine, .46; leucine, .69; lysine, .47; methionine, .13; phenylalanine, .31; threonine, .69; and valine, .54. Differences in the ranges of graded dietary levels of amino acids resulted in large differences in the estimated amounts of endogenous amino acids in ileal digesta. Furthermore, it seems that the levels of endogenous amino acids, as grams/kilogram of DMI, were constant at different dietary levels of amino acids, whereas the contributions of endogenous amino acids, as percentages of their dietary contents, decreased curvilinearly with increasing dietary contents. Therefore, apparent ileal digestibilities of amino acids were quadratically related to their dietary contents until plateau digestibilities were reached, whereas the true ileal digestibilities of amino acids were independent of their respective dietary contents. Furthermore, true ileal amino acid digestibilities should be determined from their corresponding plateau apparent ileal digestibilities. In conclusion, the levels of endogenous amino acids in ileal digesta can be determined reliably from the linear relationships between dietary contents of apparent ileal digestible and total amino acids. An important methodological consideration in the determination of endogenous amino acids by regression analysis is to design an appropriate range of graded dietary levels of amino acids.

Amino Acids↗

Prognosis for sudden sensorineural hearing loss: a retrospective study using logistical regression analysis.

Sudden sensorineural hearing loss (SSNHL) remains a controversial problem with respect to etiology and the factors that might predict prognosis. We used logistical regression analysis to determine which factors are most strongly related to outcome for patients with SSNHL. In so doing, we employed a retrospective chart-review study. The study group consisted of 296 patients (296 ears). The outcome of SSNHL was cured (full recovery) in 64, recovered (partial recovery) in 175, and no change in 57. We performed separate analyses on those in the no-change and partial-recovery groups and on those in the no-change and full-recovery groups. The following factors were studied as explanatory variables: age; number of days until presentation; vestibular symptom; initial mean hearing level at 0.25 kHz, 0.5 kHz, 1 kHz, 2 kHz, and 4 kHz; and treatments (steroids, satellite ganglion block). In the first analysis, for patients in the no-change and recovered groups, the factors most strongly related to outcome were the number of days until presentation and age. The second analysis, for the nochange and cured groups, revealed that the number of days until presentation, vestibular symptom, age, and initial mean hearing level were most strongly related to outcome. Our results will increase the ability to predict the outcome for SSNHL.

Adolescent↗

Decomposed pairwise regression analysis of genetic and geographic distances reveals a metapopulation structure of stream-dwelling Dolly Varden charr.

Isolation by distance is usually tested by the correlation of genetic and geographic distances separating all pairwise populations' combinations. However, this method can be significantly biased by only a few highly diverged populations and lose the information of individual population. To detect outlier populations and investigate the relative strengths of gene flow and genetic drift for each population, we propose a decomposed pairwise regression analysis. This analysis was applied to the well-described one-dimensional stepping-stone system of stream-dwelling Dolly Varden charr (Salvelinus malma). When genetic and geographic distances were plotted for all pairs of 17 tributary populations, the correlation was significant but weak (r(2) = 0.184). Seven outlier populations were determined based on the systematic bias of the regression residuals, followed by Akaike's information criteria. The best model, 10 populations included, showed a strong pattern of isolation by distance (r(2) = 0.758), suggesting equilibrium between gene flow and genetic drift in these populations. Each outlier population was also analysed by plotting pairwise genetic and geographic distances against the 10 nonoutlier populations, and categorized into one of the three patterns: strong genetic drift, genetic drift with a limited gene flow and a high level of gene flow. These classifications were generally consistent with a priori predictions for each population (physical barrier, population size, anthropogenic impacts). Combined the genetic analysis with field observations, Dolly Varden in this river appeared to form a mainland-island or source-sink metapopulation structure. The generality of the method will merit many types of spatial genetic analyses.

Animals↗

The effectiveness of exercise as an intervention in the management of depression: systematic review and meta-regression analysis of randomised controlled trials.

OBJECTIVE: To determine the effectiveness of exercise as an intervention in the management of depression. DESIGN: Systematic review and meta-regression analysis of randomised controlled trials obtained from five electronic databases (Medline, Embase, Sports Discus, PsycLIT, Cochrane Library) and through contact with experts in the field, bibliographic searches, and hand searches of recent copies of relevant journals. MAIN OUTCOME MEASURES: Standardised mean difference in effect size and weighted mean difference in Beck depression inventory score between exercise and no treatment and between exercise and cognitive therapy. RESULTS: All of the 14 studies analysed had important methodological weaknesses; randomisation was adequately concealed in only three studies, intention to treat analysis was undertaken in only two, and assessment of outcome was blinded in only one. The participants in most studies were community volunteers, and diagnosis was determined by their score on the Beck depression inventory. When compared with no treatment, exercise reduced symptoms of depression (standardised mean difference in effect size -1.1 (95% confidence interval -1.5 to -0.6); weighted mean difference in Beck depression inventory -7.3 (-10.0 to -4.6)). The effect size was significantly greater in those trials with shorter follow up and in two trials reported only as conference abstracts. The effect of exercise was similar to that of cognitive therapy (standardised mean difference -0.3 (95% confidence interval -0.7 to 0.1)). CONCLUSIONS: The effectiveness of exercise in reducing symptoms of depression cannot be determined because of a lack of good quality research on clinical populations with adequate follow up.

Data Collection↗